tbuckley/cabot-search huggingface dataset:
Association of Bariatric Surgery With Cardiovascular Outcomes in Adults With Severe Obesity and Nonalcoholic Fatty Liver Disease
Authors: Mohamed I. Elsaid, You Li, John F. P. Bridges, Guy Brock, Carlos D. Minacapelli, Vinod K. Rustgi
Journal: JAMA Network Open (2022)

Importance There are no approved treatments for nonalcoholic fatty liver disease (NAFLD) despite its association with obesity and increased risk of cardiovascular disease (CVD). Objective To examine the association between bariatric surgery and CVD risk in individuals with severe obesity and NAFLD. Design, Setting, and Participants This large, population-based retrospective cohort study obtained data from the MarketScan Commercial Claims and Encounters database from January 1, 2007, to December 31, 2017. Participants included insured adults aged 18 to 64 years with NAFLD and severe obesity (body mass index ≥40) without a history of bariatric surgery or CVD before NAFLD diagnosis. Baseline characteristics were balanced between individuals who underwent surgery (surgical group) and those who did not (nonsurgical group) using inverse probability of treatment weighting. Data were analyzed from March 2020 to April 2021. Exposures Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy, and other bariatric procedures) vs nonsurgical care. Main Outcomes and Measures The main outcome was the incidence of cardiovascular events (primary or secondary composite CVD outcomes). The primary composite outcome included myocardial infarction, heart failure, or ischemic stroke, and the secondary composite outcome included secondary ischemic heart events, transient ischemic attack, secondary cerebrovascular events, arterial embolism and thrombosis, or atherosclerosis. Cox proportional hazards regression models with inverse probability treatment weighting were used to examine the associations between bariatric surgery, modeled as time varying, and all outcomes. Results The study included 86 964 adults (mean [SD] age, 44.3 [10.9] years; 59 773 women [68.7%]). Of these individuals, 30 300 (34.8%) underwent bariatric surgery and 56 664 (65.2%) received nonsurgical care. All baseline covariates were balanced after applying inverse probability treatment weighting. In the surgical group, 1568 individuals experienced incident cardiovascular events compared with 7215 individuals in the nonsurgical group (incidence rate difference, 4.8 [95% CI, 4.5-5.0] per 100 person-years). At the end of the study, bariatric surgery was associated with a 49% lower risk of CVD (adjusted hazard ratio [aHR], 0.51; 95% CI, 0.48-0.54) compared with nonsurgical care. The risk of primary composite CVD outcomes was reduced by 47% (aHR, 0.53 [95% CI, 0.48-0.59), and the risk of secondary composite CVD outcomes decreased by 50% (aHR, 0.50; 95% CI, 0.46-0.53) in individuals with vs without surgery. Conclusions and Relevance Results of this study suggest that, compared with nonsurgical care, bariatric surgery was associated with significant reduction in CVD risk in individuals with severe obesity and NAFLD.
Errors in the Conflict of Interest Disclosures Statement
Journal: JAMA Network Open (2022)

Sharon Levy, MD, MPH; Lauren E. Wisk, PhD; Machiko Minegishi, MD, MSW, MPH; Benjamin Ertman, BS; Julie Lunstead, MPH; Melissa Brogna, MSW; Elissa R. Weitzman, ScD, MSc
Prevalence of Local Postoperative Complications and Breast Implant Illness in Women With Breast Implants
Authors: Annemiek S. Lieffering, Juliëtte E. Hommes, Lotte Ramerman, Hinne A. Rakhorst, Marc A. M. Mureau, Robert A. Verheij, René R. W. J. van der Hulst
Journal: JAMA Network Open (2022)

Importance It is unknown how often breast implant illness (BII) is the indication for revision in women with silicone breast implants. Objective To examine how often women with silicone breast implants have their implants explanted or replaced because of BII compared with local postoperative complications. Design, Setting, and Participants A legacy cohort study on breast implant revision surgery was conducted between April 1, 2015, and December 31, 2020, and a prospective cohort study on breast implantation and revision surgery was conducted between April 1, 2015, and December 31, 2019 (with follow-up until December 31, 2020). Data were obtained from the Dutch Breast Implant Registry. Data analysis was performed from September 2021 to August 2022. Exposures Silicone breast implant. Main Outcomes and Measures Breast implant revision with the indication BII or local postoperative complications. Results All 12 882 cosmetic breast implants (6667 women; mean [SD] age, 50.6 [12.7] years) and 2945 reconstructive breast implants (2139 women, mean [SD] age, 57.9 [11.3] years) in the legacy cohort and all 47 564 cosmetic breast implants (24 120 women, mean [SD] age, 32.3 [9.7] years) and 5928 reconstructive breast implants (4688 women, mean [SD] age, 50.9 [11.5] years) in the prospective cohort were included for analysis. In the prospective cohort, 739 cosmetic breast implants (1.6%) were revised after a median (IQR) time to reoperation of 1.8 (0.9-3.1) years, and 697 reconstructive breast implants (11.8%) were revised after a median (IQR) time to reoperation of 1.1 (0.5-1.9) years. BII was registered as the reason for revision in 35 cosmetic revisions (4.7%) and 5 reconstructive revisions (0.7%) in the prospective cohort, corresponding to 0.1% of the inserted implants. In the legacy cohort, 536 cosmetic revisions (4.2%) and 80 reconstructive breast implant revisions (2.7%) were performed because of BII. Conclusions and Relevance In this cohort study of women with silicone breast implants, BII was an uncommon indication for revision compared with local complications, both in the short and long term. In contrast to the increasing public interest in BII, these results showed that local complications are a far more common reason for breast implant revision.
Pediatric Heart Transplant Waiting List Times in the US During the COVID-19 Pandemic
Authors: John Iguidbashian, Dor Yoeli, Melanie D. Everitt, David N. Campbell, Max B. Mitchell, James Jaggers, Matthew L. Stone
Journal: JAMA Network Open (2022)

This cohort study investigates the association between the COVID-19 pandemic and waiting list times among pediatric heart transplant recipients in the US.
Association Between Preexisting Heart Failure With Reduced Ejection Fraction and Fluid Administration Among Patients With Sepsis
Authors: Rachel E. Powell, Jason N. Kennedy, Mourad H. Senussi, Ian J. Barbash, Christopher W. Seymour
Journal: JAMA Network Open (2022)

Importance Intravenous fluid administration is recommended to improve outcomes for patients with septic shock. However, there are few data on fluid administration for patients with preexisting heart failure with reduced ejection fraction (HFrEF). Objective To evaluate the association between preexisting HFrEF, guideline-recommended intravenous fluid resuscitation, and mortality among patients with community-acquired sepsis and septic shock. Design, Setting, and Participants A cohort study was conducted of adult patients hospitalized in an integrated health care system from January 1, 2013, to December 31, 2015, with community-acquired sepsis and preexisting assessment of cardiac function. Follow-up occurred through July 1, 2016. Data analyses were performed from November 1, 2020, to August 8, 2022. Exposures Preexisting heart failure with reduced ejection fraction (≤40%) measured by transthoracic echocardiogram within 1 year prior to hospitalization for sepsis. Main Outcomes and Measures Multivariable models were adjusted for patient factors and sepsis severity and clustered at the hospital level to generate adjusted odds ratios (aORs) and 95% CIs. The primary outcome was the administration of 30 mL/kg of intravenous fluid within 6 hours of sepsis onset. Secondary outcomes included in-hospital mortality, intensive care unit admission, rate of invasive mechanical ventilation, and administration of vasoactive medications. Results Of 5278 patients with sepsis (2673 men [51%]; median age, 70 years [IQR, 60-81 years]; 4349 White patients [82%]; median Sequential Organ Failure Assessment score, 4 [IQR, 3-5]), 884 (17%) had preexisting HFrEF, and 2291 (43%) met criteria for septic shock. Patients with septic shock and HFrEF were less likely to receive guideline-recommended intravenous fluid than those with septic shock without HFrEF (96 of 380 [25%] vs 699 of 1911 [37%]; P &amp;amp;lt; .001), but in-hospital mortality was similar (47 of 380 [12%] vs 244 of 1911 [13%]; P = .83). In multivariable models, HFrEF was associated with a decreased risk-adjusted odds of receiving 30 mL/kg of intravenous fluid within the first 6 hours of sepsis onset (aOR, 0.63; 95% CI, 0.47-0.85; P = .002). The risk-adjusted mortality was not significantly different among patients with HFrEF (aOR, 0.92; 95% CI, 0.69-1.24; P = .59) compared with those without, and there was no interaction with intravenous fluid volume (aOR, 1.00; 95% CI, 0.98-1.03; P = .72). Conclusions and Relevance The results of this cohort study of patients with community-acquired septic shock suggest that preexisting HFrEF was common and was associated with reduced odds of receiving guideline-recommended intravenous fluids.
Survival Benefit of First Single-Organ Deceased Donor Kidney Transplantation Compared With Long-term Dialysis Across Ages in Transplant-Eligible Patients With Kidney Failure
Authors: Susanne Strohmaier, Christine Wallisch, Michael Kammer, Angelika Geroldinger, Georg Heinze, Rainer Oberbauer, Maria C. Haller
Journal: JAMA Network Open (2022)

Importance Kidney transplant is considered beneficial in terms of survival compared with continued dialysis for patients with kidney failure. However, randomized clinical trials are infeasible, and available evidence from cohort studies is at high risk of bias. Objective To compare restricted mean survival times (RMSTs) between patients who underwent transplant and patients continuing dialysis across transplant candidate ages and depending on waiting time, applying target trial emulation methods. Design, Setting, and Participants In this retrospective cohort study, patients aged 18 years or older appearing on the wait list for their first single-organ deceased donor kidney transplant between January 1, 2000, and December 31, 2018, in Austria were evaluated. Available data were obtained from the Austrian Dialysis and Transplant Registry and Eurotransplant and included repeated updates on wait-listing status and relevant covariates. Data were analyzed between August 1, 2019, and December 23, 2021. Exposures A target trial was emulated in which patients were randomized to either receive the transplant immediately (treatment group) or to continue dialysis and never receive a transplant (control group) at each time an organ became available. Main Outcomes and Measures The primary outcome was time from transplant allocation to death. Effect sizes in terms of RMSTs were obtained using a sequential Cox approach. Results Among the 4445 included patients (2974 men [66.9%]; mean [SD] age, 52.2 [13.2] years), transplant was associated with increased survival time across all considered ages compared with continuing dialysis and remaining on the wait list within a 10-year follow-up. The estimated RMST differences were 0.57 years (95% CI, –0.14 to 1.84 years) at age 20 years, 3.01 years (95% CI, 2.50 to 3.54 years) at age 60 years, and 2.48 years (95% CI, 1.88 to 3.04 years) at age 70 years. The survival benefit for patients who underwent transplant across ages was independent of waiting time. Conclusions and Relevance The findings of this study suggest that kidney transplant prolongs the survival time of persons with kidney failure across all candidate ages and waiting times.
Prediction of Epstein-Barr Virus Status in Gastric Cancer Biopsy Specimens Using a Deep Learning Algorithm
Authors: Trinh Thi Le Vuong, Boram Song, Jin T. Kwak, Kyungeun Kim
Journal: JAMA Network Open (2022)

Importance Epstein-Barr virus (EBV)–associated gastric cancer (EBV-GC) is 1 of 4 molecular subtypes of GC and is confirmed by an expensive molecular test, EBV-encoded small RNA in situ hybridization. EBV-GC has 2 histologic characteristics, lymphoid stroma and lace-like tumor pattern, but projecting EBV-GC at biopsy is difficult even for experienced pathologists. Objective To develop and validate a deep learning algorithm to predict EBV status from pathology images of GC biopsy. Design, Setting, and Participants This diagnostic study developed a deep learning classifier to predict EBV-GC using image patches of tissue microarray (TMA) and whole slide images (WSIs) of GC and applied it to GC biopsy specimens from GCs diagnosed at Kangbuk Samsung Hospital between 2011 and 2020. For a quantitative evaluation and EBV-GC prediction on biopsy specimens, the area of each class and the fraction in total tissue or tumor area were calculated. Data were analyzed from March 5, 2021, to February 10, 2022. Main Outcomes and Measures Evaluation metrics of predictive model performance were assessed on accuracy, recall, precision, F1 score, area under the receiver operating characteristic curve (AUC), and κ coefficient. Results This study included 137 184 image patches from 16 TMAs (708 tissue cores), 24 WSIs, and 286 biopsy images of GC. The classifier was able to classify EBV-GC image patches from TMAs and WSIs with 94.70% accuracy, 0.936 recall, 0.938 precision, 0.937 F1 score, and 0.909 κ coefficient. The classifier was used for predicting and measuring the area and fraction of EBV-GC on biopsy tissue specimens. A 10% cutoff value for the predicted fraction of EBV-GC to tissue (EBV-GC/tissue area) produced the best prediction results in EBV-GC biopsy specimens and showed the highest AUC value (0.8723; 95% CI, 0.7560-0.9501). That cutoff also obtained high sensitivity (0.895) and moderate specificity (0.745) compared with experienced pathologist sensitivity (0.842) and specificity (0.854) when using the presence of lymphoid stroma and a lace-like pattern as diagnostic criteria. On prediction maps, EBV-GCs with lace-like pattern and lymphoid stroma showed the same prediction results as EBV-GC, but cases lacking these histologic features revealed heterogeneous prediction results of EBV-GC and non–EBV-GC areas. Conclusions and Relevance This study showed the feasibility of EBV-GC prediction using a deep learning algorithm, even in biopsy samples. Use of such an image-based classifier before a confirmatory molecular test will reduce costs and tissue waste.
A germline STAT6 gain-of-function variant is associated with early-onset allergies
Authors: Narissara Suratannon, Chupong Ittiwut, Willem A. Dik, Rungnapa Ittiwut, Kornvalee Meesilpavikkai, Nipan Israsena, Praewphan Ingrungruanglert, Virgil A.S. H. Dalm, Paul L.A. van Daele, Anapat Sanpavat, Nataruks Chaijitraruch, Benjamin Schrijver, Supranee Buranapraditkun, Thantrira Porntaveetus, Sigrid M.A. Swagemakers, Hanna IJspeert, Tanapat Palaga, Kanya Suphapeetiporn, Peter J. van der Spek, Nattiya Hirankarn, Pantipa Chatchatee, P. Martin van Hagen, Vorasuk Shotelersuk
Journal: Journal of Allergy and Clinical Immunology (2022)
Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection
Authors: Krist Helen Antunes, Aran Singanayagam, Lily Williams, Tasnim Syakirah Faiez, Ana Farias, Millie M Jackson, Fatima K Faizi, Julia Aniscenko, Tatiana Kebadze, Punnam Chander Veerati, Lisa Wood, Nathan W Bartlett, Ana Paula Duarte de Souza, Sebastian L Johnston
Journal: Journal of Allergy and Clinical Immunology (2022)

BackgroundMicrobiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated.ObjectiveWe sought to investigate whether pulmonary metabolite manipulation through lung-delivered administration of SCFAs can modulate antiviral immunity to RV infection.MethodsWe studied the effects of intranasal administration of the SCFAs acetate, butyrate, and propionate on basal expression of antiviral signatures, and of acetate in a mouse model of RV infection and in RV-infected lung epithelial cell lines. We additionally assessed the effects of acetate, butyrate, and propionate on RV infection in differentiated human primary bronchial epithelial cells.ResultsIntranasal acetate administration induced basal upregulation of IFN-β, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-λ expression during RV infection and reduced lung virus loads at 8 hours postinfection. Acetate ameliorated virus-induced proinflammatory responses with attenuated pulmonary mucin and IL-6 expression observed at day 4 and 6 postinfection. This interferon-enhancing effect of acetate was confirmed in human bronchial and alveolar epithelial cell lines. In differentiated primary bronchial epithelial cells, butyrate treatment better modulated IFN-β and IFN-λ gene expression during RV infection.ConclusionsSCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection.Graphical abstract
Genomes of Two Flying Squid Species Provide Novel Insights into Adaptations of Cephalopods to Pelagic Life
Authors: Min Li, Baosheng Wu, Peng Zhang, Ye Li, Wenjie Xu, Kun Wang, Qiang Qiu, Jun Zhang, Jie Li, Chi Zhang, Jiangtao Fan, Chenguang Feng, Zuozhi Chen
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Pelagic cephalopods have evolved a series of fascinating traits, such as excellent visual acuity, high-speed agility, and photophores for adaptation to open pelagic oceans. However, the genetic mechanisms underpinning these traits are not well understood. Thus, in this study, we obtained high-quality genomes of two purpleback flying squid species (Sthenoteuthis oualaniensis and Sthenoteuthis sp.), with sizes of 5450 Mb and 5651 Mb, respectively. Comparative genomic analyses revealed that the S-crystallin subfamily SL20-1 associated with visual acuity in the purpleback flying squid lineage was significantly expanded, and the evolution of high-speed agility for the species was accompanied by significant positive selection pressure on genes related to energy metabolism. These molecular signals might have contributed to the evolution of their adaptative predatory and anti-predatory traits. In addition, the transcriptomic analysis provided clear indications of the evolution of the photophores of purpleback flying squids, especially the recruitment of new genes and energy metabolism-related genes which may have played key functional roles in the process.
Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite <i>Toxoplasma Gondii</i>
Authors: Deqi Yin, Ning Jiang, Chang Cheng, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract The biology of Toxoplasma gondii, the causative pathogen of one of the most widespread parasitic diseases (toxoplasmosis), remains poorly understood. Lactate, which is derived from glucose metabolism, is not only an energy source in a variety of organisms, including T. gondii, but also a regulatory molecule that participates in gene activation and protein function. Lysine lactylation (Kla) is a type of post-translational modifications (PTMs) that has been recently associated with chromatin remodeling; however, Kla of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and identified 1964 Kla sites on 955 proteins in the T. gondii RH strain. Lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and many signaling pathways. We also performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis using a lactylation-specific antibody and found that the histones H4K12la and H3K14la were enriched in the promoter and exon regions of T. gondii associated with microtubule-based movement and cell invasion. We further confirmed the delactylase activity of histone deacetylases TgHDAC2–4, and found that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in T. gondii. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T. gondii.
SOPHIE: Generative Neural Networks Separate Common and Specific Transcriptional Responses
Authors: Alexandra J. Lee, Dallas L. Mould, Jake Crawford, Dongbo Hu, Rani K. Powers, Georgia Doing, James C. Costello, Deborah A. Hogan, Casey S. Greene
Journal: Genomics Proteomics & Bioinformatics (2022)

Genome-wide transcriptome profiling identifies genes that are prone to differential expression (DE) across contexts, as well as genes with changes specific to the experimental manipulation. Distinguishing genes that are specifically changed in a context of interest from common differentially expressed genes (DEGs) allows more efficient prediction of which genes are specific to a given biological process under scrutiny. Currently, common DEGs or pathways can only be identified through the laborious manual curation of experiments, an inordinately time-consuming endeavor. Here we pioneer an approach, Specific cOntext Pattern Highlighting In Expression data (SOPHIE), for distinguishing between common and specific transcriptional patterns using a generative neural network to create a background set of experiments from which a null distribution of gene and pathway changes can be generated. We apply SOPHIE to diverse datasets including those from human, human cancer, and bacterial pathogen Pseudomonas aeruginosa. SOPHIE identifies common DEGs in concordance with previously described, manually and systematically determined common DEGs. Further molecular validation indicates that SOPHIE detects highly specific but low-magnitude biologically relevant transcriptional changes. SOPHIE's measure of specificity can complement log
DermX: An end-to-end framework for explainable automated dermatological diagnosis
Authors: Raluca Jalaboi, Frederik Faye, Mauricio Orbes-Arteaga, Dan Jørgensen, Ole Winther, Alfiia Galimzianova
Journal: Medical Image Analysis (2022)

Dermatological diagnosis automation is essential in addressing the high prevalence of skin diseases and critical shortage of dermatologists. Despite approaching expert-level diagnosis performance, convolutional neural network (ConvNet) adoption in clinical practice is impeded by their limited explainability, and by subjective, expensive explainability validations. We introduce DermX, an end-to-end framework for explainable automated dermatological diagnosis. DermX is a clinically-inspired explainable dermatological diagnosis ConvNet, trained using DermXDB, a 554 image dataset annotated by eight dermatologists with diagnoses, supporting explanations, and explanation attention maps. DermX+ extends DermX with guided attention training for explanation attention maps. Both methods achieve near-expert diagnosis performance, with DermX, DermX+, and dermatologist F1 scores of 0.79, 0.79, and 0.87, respectively. We assess the explanation performance in terms of identification and localization by comparing model-selected with dermatologist-selected explanations, and gradient-weighted class-activation maps with dermatologist explanation maps, respectively. DermX obtained an identification F1 score of 0.77, while DermX+ obtained 0.79. The localization F1 score is 0.39 for DermX and 0.35 for DermX+. These results show that explainability does not necessarily come at the expense of predictive power, as our high-performance models provide expert-inspired explanations for their diagnoses without lowering their diagnosis performance.